Osterrieder Identifies Key Gene in Equine Herpes Virus
Equine herpes virus type 1 (EHV-1) causes disease in horses worldwide. In its early stages, the virus usually triggers a fever and respiratory problems. The horse initially may have trouble breathing, shortness of breath (dyspnoea), or cough excessively. As the infection takes root, the virus can cause serious problems in the reproductive, respiratory, or central nervous systems. It can trigger abortions in pregnant mares and a respiratory disease called rhinopneumonitis, which occurs mostly in young horses. And, owing to nerve damage, it can cause neurological difficulties such as paralysis of the back legs or bladder problems.
EHV-1 is particularly contagious early in the infection and can spread quickly during outbreaks via droplets in the air or from equipment that's been used recently by an infected and virus-shedding horse.
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Osterrieder uses fluorescent technology to track the equine herpes virus type 1 as it moves through an animal's body. Pictured here is a virus plaque - the empty space that's left behind after the virus has killed cells. |
“More recently, the neurological form of the disease has been predominant and has caused considerable losses to the equine industry,” says Klaus Osterrieder, DVM, who came to the college from Germany in mid-2002 as an associate professor of virology. “In devastating recent outbreaks of EHV-1 in herds, studs, and at racetracks, an unusually high number of horses exhibited the neurological form of the disease. This is alarming because this form of EHV-1 infection used to be sporadic and contained to individual animals of an affected herd. Recent reports, however, suggest the emergence of a high percentage of affected horses developing severe clinical disease, with some herds experiencing a 90 percent morbidity and more than 10 percent mortality rate.”
“Another striking feature of these recent outbreaks is that many horses got seriously ill despite regular vaccinations in very short intervals. Clearly, we need better vaccines and vaccine protocols,” Osterrieder adds.
For over ten years, Osterrieder has been working on these viruses with the end goal of developing an effective vaccine that is not so pathogenic that it causes severe symptoms but is effective enough to prevent infection.
So far, he has identified a gene that is absent from a particular herpes virus vaccine strain and actually expresses a protein that is absolutely required to cause a disease state. This was a major step toward understanding what is needed for a more effective vaccine.
It is generally accepted that the virus launches its attack by infecting the endothelia—the inner lining cells—of small blood vessels. This assault inflames the blood vessels (vasculitis) and causes blood clots (thrombosis). The clots, in turn, interfere with the blood flow (microcirculation) in the affected area, depriving the area of adequate oxygen (hypoxia) and soon leading to nerve damage and nerve death. This same process of inflammation, clot formations, and oxygen deprivation can cause placentas to detach and cause malnutrition in a fetus. Osterrieder's laboratory had determined that certain proteins of the EHV-1 membrane were involved crucially in the early stages of infection and in the virus's ability to spread.
With funding from the Zweig Memorial Fund, Osterrieder compared a strain of herpes virus that did not trigger disease with a wild herpes virus strain that did cause disease to try to pinpoint which protein made the critical difference. He targeted a certain spot and swapped a gene from the virulent strain that he thought "Recent reports, however, suggest the emergence of a high percentage of affected horses developing severe clinical disease, with some herds experiencing a 90 percent morbidity and more than 10 percent mortality rate.”
- Klaus Osterriedermight be the culprit and put it into the strain that didn't cause disease—the avirulent strain, thereby making a mutant strain. Together with his longtime collaborators, Drs. Dennis O'Callaghan and Patrick Smith from the Louisiana State Health Sciences Center, Osterrieder then tested this mutant strain in two different lines of mice to see if the protein-modified avirulent strain would now cause disease. (In studies such as these, the mouse is a good research model for the horse.)
“When we tested the strain in mice, it turned out to be very deadly in one line of mice but basically avirulent in the other,” says Osterrieder. “It behaved so differently in the two strains of mice that we think it might make a good candidate for a vaccine. That's because the generated mutant virus may not be overly attenuated, which sometimes is counterproductive in terms of protection against circulating field viruses.”
The next step in vaccine virus testing, however, is very difficult: to assess the mutant strain's protective capabilities in horses.
“We must find a group of horses that has never been exposed to strains of the equine herpes virus, which is very difficult because most horses have been exposed,” says Osterrieder. He hopes to find herpes-negative horses by testing horses at auctions. He plans to buy any negative horses available with the hope of having a group to test by the end of the year.
If that doesn't work out, Osterrieder may obtain horses from Canada where the horse population is much less dense. Another option is to test horses that have been exposed but not in the very recent past and haven't developed a full-blown infection. Those are the horses that many veterinarians would encounter and vaccinate anyway and, as such, are a reflection of the real-world situation.
So far, Osterrieder's research has focused on the EHV strain that has been isolated for more than 50 years and the virus against which current vaccines presumably protect. He hopes to be able to obtain isolates that have been causing the severe outbreaks recently.
“We will have to determine if the new strains, in fact, are really different from the virus we're more familiar with,” says Osterrieder. He says that preliminary evidence suggests that the strains vary minimally and that it's not mutations of the virus that have caused the recent severe outbreaks, but changes in animal husbandry practices. 
